Combined Application of Sodium Fluorescein and Neuronavigation Techniques in the Resection of Brain Gliomas

Objectives: To explore the effectiveness and safety of the combined application of sodium fluorescein and neuronavigation techniques in the resection of brain gliomas in different locations and patients of different ages.Methods: Fifty clinical cases of brain gliomas treated at the Department of Neurosurgery of Beijing Tiantan Hospital were collected from March 2014 to March 2019. These cases were divided into a supratentorial group (24 cases) and a brainstem group (26 cases) based on location and an adult group (28 cases) and a pediatric group (22 cases) based on age. Fluorescein-guided surgery was performed: the adult group received 5 mg/kg sodium fluorescein before opening the dura, while the pediatric group received 2.5 mg/kg during resection. Tumor visualization was evaluated by the enhancement of yellow fluorescein and considered “satisfactory” if the illumination demarcated the tumor boundary. Additionally, the consistency between fluorescein and neuronavigation was analyzed. The Karnofsky performance score (KPS) of all patients was recorded and assessed at admission, discharge, and the 6-month follow-up.Results: In the 28 adult cases, 4 were unsatisfactory, while in the 22 pediatric cases, 2 were unsatisfactory; in 7 cases, there was an inconsistency between yellow fluorescein enhancement and neuronavigation, 6 were in the supratentorial group, and 1 was in the brainstem group. Statistical analysis showed no significant differences in the satisfactory rate between the adult and pediatric groups (P = 0.575), whereas there were significant differences inconsistency between the supratentorial group and brainstem group (P = 0.031). The mean KPS at admission was between 70 and 100, which was not significantly different from that at discharge (P = 0.839), but the KPS at the 6-month follow-up was significantly higher than that at admission (P = 0.041).Conclusions: The consistency between sodium fluorescein and the neuronavigation system was higher in the brainstem group than in the supratentorial group; a half dose of sodium fluorescein (2.5 mg/kg) was sufficient for pediatric patients. The combined utilization of sodium fluorescein and neuronavigation techniques may confer glioma patients the opportunity to obtain better clinical outcomes after surgery.

Supratotal Resection of Periventricular Glioblastomas and Pathomorphological Rationale for Extensive Removal of Subventricular Zone

The aim of the research was to reveal the pathomorphological patterns of periventricular glioblastoma (PVG) dissemination and assess the rationale for extended surgical removal of subventricular zone (SVZ) as a step towards supratotal resection.A total of 54 patients (16 females and 38 males, mean age 48.9 ± 13.4 years, range 22–69) with PVG were prospectively included in the study. Standard preoperative evaluation included an MRI using 3D T1 with Gd-enhancement, T2, and T2-FLAIR series. The neuronavigation system was used to identify the SVZ and to remove of ventricular wall, additionally to image-guided total tumor resection. The pathomorphological assessment of PVG features with the description of the SVZ and changes in perifocal brain matter was performed by two pathologists.The median Karnofsky Performance Scale (KPS) score raised from 67.8 to 81.9 in the postoperative period. The overall median survival was 13.0 ± 2.7 months. The low postoperative KPS score (p = 0.05) and basal ganglia invasion (p = 0.008) significantly decreased survival rates.Microscopically, the typical multilayer structure of SVZ was disrupted. The invasive spread of tumor cells in thesubventricular space was identified. The ependymal layer had prominent dystrophic alterations of cells and destruction of intracellular connections. The hyperplastic reaction on neoplastic process was typical for adjacent ependyma.The pathomorphological identification of periventricular glioblastoma invasion in the subependymal space supports the supratotal tumor resection with removal of adjacent SVZ as a potential source for relapse.

PATH-43. RAMAN SPECTROSCOPY AS A TOOL IN NEUROSURGERY

BACKGROUND Raman Spectra have been shown to be sufficiently characteristic to their samples of origin that they can be used in a wide range of applications including distinction of intracranial tumors. While not replacing pathological analysis, the advantage of non-destructive sample analysis and extremely fast feedback make this technique an interesting tool for surgical use. METHODS We sampled intractanial tumors from more than 300 patients at the Centre Hospitalier Luxembourg over a period of three years and compared the spectra of different tumor entities, different tumor subregions and healthy surrounding tissue. We created machine-learning based classifiers that include tissue identification as well as diagnostics. RESULTS To this end, we solved several classes in the intracranial tumor classification, and developed classifiers to distinguish primary central nervous system lymphoma from glioblastoma, which is an important differential diagnosis, as well as meningioma from the surrounding healthy dura mater for identification of tumor tissue. Within glioblastoma, we resolve necrotic, vital tumor tissue and peritumoral infiltration zone.We are currently developing a multi-class classifier incorporating all tissue types measured. CONCLUSIONS Raman Spectroscopy has the potential to aid the surgeon in the surgery theater by providing a quick assessment of the tissue analyzed with regards to both tumor identity and tumor margin identification. Once a reliable classifier based on sufficient patient samples is developed, this may even be integrated into a surgical microscope or a neuronavigation system.

ITVT-04. Management of intraoperative technological advances [intraoperative MRI, neuronavigation system using PET, and 5-aminolevulinic acid (5-ALA)–induced fluorescence image-guided surgery] for glioblastoma

OBJECTIVE The maximum resection of Glioblastoma (GBM) is the standard therapy and is expected to improve prognosis. Image-guided surgery using a neuronavigation system is the standard technique for glioma. However, due to the brain shift during surgery, intraoperative technologies, such as 5-ALA fluorescence and intraoperative MRI (IoMRI), are employed. Radiotracers are used during positron emission tomography (PET) for metabolic imaging and assist the evaluation of glioma metabolism. We compared the effectiveness of these intraoperative technologies. METHODS Between January 2016 and May 2021, 52 patients with gliomas underwent IoMRI. 21 patients were selected for 5-ALA fluorescence-guided resection of GBM and underwent multiple PET studies (MET, FLT, and FMISO). We graded fluorescence level as strong, vague, or none. Following tumor resection, we identified the fluorescence level and evaluated the residual volume of gadolinium-enhanced T1WI (T1-Gd) on IoMRI and at each PET study. After calculating the extent of resection (EOR) for T1-Gd, we compared the residual volume on T1-Gd for IoMRI and each PET study, between EOR ≥ 93% and EOR < 93%. RESULTS We detected strong 5-ALA fluorescence during induction and before tumor resection in all 21 (100%) patients with a newly-diagnosed and histopathologically-confirmed GBM. Following tumor resection, we noted an EOR ≥ 93% for T1-Gd in 12 cases (vague, 4; none, 8) and an EOR < 93% for T1-Gd in 9 cases (vague, 5; none, 4). The compared median residual volume (mL) with no fluorescence between EOR ≥ 93% and EOR < 93% for T1-Gd were T1-Gd (0.22, 0.74), MET (0.29, 3.31), FLT (0.24, 1.77), and FMISO (0.22, 1.02). CONCLUSIONS GBM cells are difficult to distinguish in cases without 5-ALA fluorescence. For cases without 5-ALA fluorescence, we were able to maximize the resection of GBM by extracting the area of MET accumulation.

Comparative Study between Neuro-navigation and Intra-Operative Ultrasound in Excision of Intra-axial Brain Lesions

Background The application of imaging during surgery can improve patient outcomes by accurate and thorough removal of lesions while having minimal impact on healthy tissue. Aim of the Work to compare the use of neuronavigation to intraoperative ultrasound guidance in excision of intra-axial brain lesion. Patients and Methods This cohort study was conducted on 51 patients with intra-axial brain lesion is amenable to gross total resection. The primary outcome was extent of resection assessed using a non-volumetric technique. Other outcomes included the postoperative functional status and the rate of operative complications. Results There were 34 patients in the Neuronavigation group and 17 patients in the ultrasound group. The extent of resection was significantly better in the ultrasound group as the extent of tumor resection based on the GTR/NTR/STR method of assessment showed that the IOUS group had statistically significant higher chance of achieving GTR (29.4%) than the navigation group (8.8%). In the IOUS group near total and subtotal resection rates were 17% and 52% respectively. In neuronavigation group 11.8% and 79.4%. Conclusion application of ultrasound integrated in Neuronavigation system guidance in surgery excision of intra-axial brain lesions is a useful tool in achieving a higher extent of tumor resection (EOR).

Transopercular Insular Approach, Overcoming the Training Curve Using a Cadaveric Simulation Model: 2-Dimensional Operative Video

Transopercular approach to the insula is indicated for resection of insular low-grade gliomas, particularly for Yasargil's 3B, 5A, and 5B types. Nevertheless, the infrequent location and its challenging approach make it difficult to master the surgery. Consequently, a realistic laboratory training model might help to acquire key surgical skills. In this video, we describe a cadaveric-based model simulating the resection of a temporo-insular low-grade glioma. Kingler's fixation technique was used to fix the cadaver head before injecting red and blue colorants for a realistic vascular appearance. Hemisphere was frozen for white matter tract dissection. Tractography and intraoperative eloquent areas were extrapolated from a glioma patient by using a neuronavigation system. Then, a fronto-temporal craniotomy was performed through a question mark incision, exposing from inferior temporal gyrus up to middle frontal gyrus. After cortical anatomic landmark identification, eloquent areas were extrapolated creating a simulated functional cortical map. Then, transopercular noneloquent frontal and temporal corticectomies were performed, followed by subpial resection. Detailed identification of Sylvian vessels and insular cortex was demonstrated. Anatomic resection limits were exposed, and implicated white matter bundles, uncinate and fronto-occipital fascicles, were identified running through the temporal isthmus. Finally, a temporo-mesial resection was performed. In summary, this model provides a simple, cost-effective, and very realistic simulation of a transopercular approach to the insula, allowing the development of surgical skills needed to treat insular tumors in a safe environment. Besides, the integration of simulated navigation has proven useful in better understanding the complex white matter anatomy involved. Cadaver donation, subject or relatives, includes full consent for publication of the images. For the purpose of this video, no ethics committee approval was needed. Images correspond to a cadaver head donation. Cadaver donation, subject or relatives, includes full consent for any scientific purposes involving the corpse. The consent includes image or video recording. Regarding the intraoperative surgical video and tractography, the patient gave written consent for scientific divulgation prior to surgery.

Coplanar Indirect-Navigated Intraoperative Ultrasound: Matching Un-navigated Probes With Neuronavigation During Neurosurgical Procedures. How We Do It

BACKGROUND Intraoperative ultrasound (IOUS) is becoming more and more adopted in neurosurgery, since it has been associated to greater extent of resection (EOR) and to gross total resection (GTR) during brain tumor surgery. IOUS main limitations are spatial resolution, width and orientation of the field of view and scan quality, which are operator-dependent. Furthermore, most neurosurgeons are not confident with this technique, which needs a long learning curve in order to identify and interpret anatomic structures. OBJECTIVE To describe an effective procedure to take advantages of both IOUS and neuronavigation in case of lack of a navigated ultrasound system. METHODS We propose a reliable “indirect-navigated” technique which is based on the optical tracking of un-navigated IOUS probe by the use of a multipurpose passive tracker and a proper configuration of common neuronavigation system. RESULTS Navigated IOUS is not available in all neurosurgical operating rooms but ultrasound systems are common tools in many hospital facilities and neuronavigation systems are common in almost all the neurosurgical operating rooms. The proposed indirect-navigated technique shows some paramount advantages: since almost all the neurosurgical operating rooms are provided with a neuronavigation system, the only tool needed is the ultrasonography. Therefore, this procedure is largely accessible and costless, reliable, and may improve the neurosurgeon's ability in ultrasonographic anatomy. CONCLUSION This technique is based on the coplanar and coupled use of both un-navigated IOUS probe and standard optical neuronavigation, in order to allow the intraoperative navigation of IOUS images when a navigated ultrasound system is not available.

A functional ultrasound brain GPS for automatic vascular-based neuronavigation

Recent advances in ultrasound imaging triggered by transmission of ultrafast plane waves have rendered functional ultrasound (fUS) imaging a valuable neuroimaging modality capable of mapping cerebral vascular networks, but also for the indirect capture of neuronal activity with high sensitivity thanks to the neurovascular coupling. However, the expansion of fUS imaging is still limited by the difficulty to identify cerebral structures during experiments based solely on the Doppler images and the shape of the vessels. In order to tackle this challenge, this study introduces the vascular brain positioning system (BPS), a GPS of the brain. The BPS is a whole-brain neuronavigation system based on the on-the-fly automatic alignment of ultrafast ultrasensitive transcranial Power Doppler volumic images to common templates such as the Allen Mouse Brain Common Coordinates Framework. This method relies on the online registration of the complex cerebral vascular fingerprint of the studied animal to a pre-aligned reference vascular atlas, thus allowing rapid matching and identification of brain structures. We quantified the accuracy of the automatic registration using super-resolution vascular images obtained at the microscopic scale using Ultrasound Localization Microscopy and found a positioning error of 44 µm and 96 µm for intra-animal and inter-animal vascular registration, respectively. The proposed BPS approach outperforms the manual vascular landmark recognition performed by expert neuroscientists (inter-annotator errors of 215 µm and 259 µm). Using the online BPS approach coupled with the Allen Atlas, we demonstrated the capability of the system to position itself automatically over chosen anatomical structures and to obtain corresponding functional activation maps even in complex oblique planes. Finally, we show that the system can be used to acquire and estimate functional connectivity matrices automatically. The proposed functional ultrasound on-the-fly neuronavigation approach allows automatic brain navigation and could become a key asset to ensure standardized experiments and protocols for non-expert and expert researchers.

Utility of a novel exoscope, ORBEYE, in gravity-assisted brain retraction surgery for midline lesions of the brain

Background: Midline brain lesions, such as falx meningioma, arteriovenous malformations, and cavernous malformations, are usually approached from the ipsilateral interhemispheric fissure. To this end, patients are positioned laterally with the ipsilateral side up. However, some studies have reported the usefulness of gravity-assisted brain retraction surgery, in which patients are placed laterally with the ipsilateral side down or up, enabling surgeons to approach the lesions through the ipsilateral side or through a contralateral interhemispheric fissure, respectively. This surgery requires less brain retraction. However, when using an operative microscope, performing this surgery requires the surgeon to operate in an awkward position. A recently developed high-definition (4K-HD) 3-D exoscope system, ORBEYE, can improve the surgeon’s posture while performing gravity-assisted brain retraction surgery. Methods: We report five cases with midline brain tumors managed by resectioning with gravity-assisted brain retraction surgery using ORBEYE. We also performed an ergonomic analysis of gravity-assisted brain retraction surgery with a craniotomy model and a neuronavigation system. Results: Gravity-assisted brain retraction surgery to the midline brain tumors was successfully performed for all five patients, using ORBEYE, without any postoperative neurological deficit. Conclusion: Gravity-assisted brain retraction surgery to the midline brain lesions using ORBEYE is feasible, and ORBEYE is ergonomically more favorable than a microscope. ORBEYE has the potential to generalize neurosurgical approaches considered difficult due to the surgeon’s awkward position, such as gravity-assisted brain retraction surgery.